This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Worldwide, the vast majority of HIV-1 cases occur through heterosexual transmission. Although the initial events involved in vaginal transmission are uncertain, studies suggest that dendritic cells in the vaginal epithelium may be involved in trapping viral particles on the surface and transporting them to CD4+ T lymphocytes in the mucosa. As a collaborative, multicenter trial with the Center for HIV and AIDS vaccine Initiative (CHAVI) we are continuing studies to determine the earliest target cells and events involved in vaginal HIV transmission using the macaque model of SIV/HIV transmission. Our prior studies indicated that HIV enters the squamous epithelium of the vagina by a passive, non-cellular mechanisms (simple diffusion) and we are currently examining the integrity and distribution of various tight junction proteins in the vagina to determine whether these differ from other squamous epithelia. We are also comparing the uptake of nanoparticles and env deficient virus to prove that these are non-specific mechanisms of uptake. These technologies will help to develop better vaccine and microbicide strategies.